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Mutant Gq/11 promote uveal melanoma tumorigenesis by activating YAP.

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机构： [1]Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA [2]Department of Ophthalmology and Shiley Eye Center and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA [3]Department of Ophthalmology of the Second Xiangya Hospital, International Academy of Translational Medicine, Central South University, Changsha 410011, China [4]Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [5]Arizona Retinal Specialists, Sun City West, AZ 85375, USA [6]Departments of Dermatology and Pathology and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA [7]Department of Nanoengineering, University of California, San Diego, La Jolla, CA 92093, USA [8]Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, University of California, Los Angeles, School of Dentistry, Los Angeles, CA 90095, USA [9]Veterans Administration Healthcare System, San Diego, CA 92161, USA

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Uveal melanoma (UM) is the most common cancer in adult eyes. Approximately 80% of UMs harbor somatic activating mutations in GNAQ or GNA11 (encoding Gq or G11, respectively). Herein, we show in both cell culture and human tumors that cancer-associated Gq/11 mutants activate YAP, a major effector of the Hippo tumor suppressor pathway that is also regulated by G protein-coupled receptor signaling. YAP mediates the oncogenic activity of mutant Gq/11 in UM development, and the YAP inhibitor verteporfin blocks tumor growth of UM cells containing Gq/11 mutations. This study reveals an essential role of the Hippo-YAP pathway in Gq/11-induced tumorigenesis and suggests YAP as a potential drug target for UM patients carrying mutations in GNAQ or GNA11. Copyright © 2014 Elsevier Inc. All rights reserved.

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出版当年[2014]版：

大类 | 1 区

医学

小类 | 1 区细胞生物学 1 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区细胞生物学 1 区肿瘤学

第一作者：

第一作者机构： [1]Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA

通讯作者：

通讯机构： [2]Department of Ophthalmology and Shiley Eye Center and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA [3]Department of Ophthalmology of the Second Xiangya Hospital, International Academy of Translational Medicine, Central South University, Changsha 410011, China [4]Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [9]Veterans Administration Healthcare System, San Diego, CA 92161, USA

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